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Genes Dev. 2015 Mar 15;29(6):585-90. doi: 10.1101/gad.256354.114.

Two distinct modes for propagation of histone PTMs across the cell cycle.

Author information

1
Biotech Research and Innovation Centre (BRIC), University of Copenhagen, 2200 Copenhagen, Denmark; Centre for Epigenetics, University of Copenhagen, 2200 Copenhagen, Denmark;
2
Munich Centre of Integrated Protein Science, Ludwig-Maximillians University of Munich, 80336 Munich, Germany; Adolf Butenandt Institute, Ludwig-Maximillians University of Munich, 80336 Munich, Germany;
3
Centre for Epigenetics, University of Copenhagen, 2200 Copenhagen, Denmark; Department of Biochemistry and Molecular Biology, University of Southern Denmark, DK-5230 Odense, Denmark.
4
Munich Centre of Integrated Protein Science, Ludwig-Maximillians University of Munich, 80336 Munich, Germany; Adolf Butenandt Institute, Ludwig-Maximillians University of Munich, 80336 Munich, Germany; imhof@lmu.de anja.groth@bric.ku.dk.
5
Biotech Research and Innovation Centre (BRIC), University of Copenhagen, 2200 Copenhagen, Denmark; Centre for Epigenetics, University of Copenhagen, 2200 Copenhagen, Denmark; imhof@lmu.de anja.groth@bric.ku.dk.

Abstract

Epigenetic states defined by chromatin can be maintained through mitotic cell division. However, it remains unknown how histone-based information is transmitted. Here we combine nascent chromatin capture (NCC) and triple-SILAC (stable isotope labeling with amino acids in cell culture) labeling to track histone modifications and histone variants during DNA replication and across the cell cycle. We show that post-translational modifications (PTMs) are transmitted with parental histones to newly replicated DNA. Di- and trimethylation marks are diluted twofold upon DNA replication, as a consequence of new histone deposition. Importantly, within one cell cycle, all PTMs are restored. In general, new histones are modified to mirror the parental histones. However, H3K9 trimethylation (H3K9me3) and H3K27me3 are propagated by continuous modification of parental and new histones because the establishment of these marks extends over several cell generations. Together, our results reveal how histone marks propagate and demonstrate that chromatin states oscillate within the cell cycle.

KEYWORDS:

DNA replication; cell cycle; epigenetics; histone post-translational modifications; histone recycling; histone variants

PMID:
25792596
PMCID:
PMC4378191
DOI:
10.1101/gad.256354.114
[Indexed for MEDLINE]
Free PMC Article

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